Preparation, in vitro and in vivo evaluation of polymeric nanoparticles bas hyaluronic acid-poly(but

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Herein,wedescribethepreparationofatargetedcellulardeliverysystemformorinhydrate(MH),-molecular-weighthyaluronicacid-poly(butylcyanoacrylate)(HA-PBCA)blockcopolymer.InordthetherapeuticeffectofMH,D-alpha-tocopherylpolyethyleneglycol1000succinate(TPGS)wasHA-PBCAduringthepreparationprocess.TheMH-loadedHA-PBCA“plain”nanoparticle(MH-PPBCA/TPGS“mixed”nanoparticles(MH-MNs)wereconcomitantlycharacterizedintermsofloadparticlesize,zetapotential,criticalaggregationconcentration,andmorphology.TheobtainedMHMNsexhibitedasphericalmorphologywithanegativezetapotentialandaparticlesizelessthan2favorablefordrugtargeting.Remarkably,theadditionofTPGSresultedinabout1.6-foldincreaseloading.TheinvitrocellviabilityexperimentrevealedthatMH-MNsenhancedthecytotoxicityofcellscomparedwithMHsolutionandMH-PNs.Furthermore,blankMNscontainingTPGSexhibitcytotoxiceffectsagainstcancercellswithoutdiminishingtheviabilityofnormalcells.Inaddition,uptakestudyindicatedthatMNsresultedin2.28-foldhighercellularuptakethanthatofPNs,inA5CD44receptorcompetitiveinhibitionandtheinternalizationpathwaystudiessuggestedthattheintmechanismofthenanoparticleswasmediatedmainlybytheCD44receptorsthroughaclathrin-dependocyticpathway.Moreimportantly,MH-MNsexhibitedahigherinvivoantitumorpotencyandtumorcellapoptosisthandidMH-PNs,followingintravenousadministrationtoS180tumor-bearinOverall,theresultsimplythatthedevelopednanoparticlesarepromisingvehiclesforthetargeteddlipophilicanticancerdrugs.Keywords:anti-tumoreffect,hyaluronicacid,TPGS,morinhydrate,nanoparticles
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